Identification and characterization of a putative tumor suppressor gene ANXA10 in gastric carcinoma

Abstract

Genetic alterations are observed as important event in gastric carcinogenesis. In the present study, array based comparative genomic hybridization (CGH) was used to screen DNA copy number change in gastric cancer cell lines and the results obtained were compared with oligonucleotide microarray data. Novel genes that are related to human gastric cancer were identified using genome-wide screening. DNA loss of the Annexin A10 (ANXA10) locus in chromosome 4q33 was found in several gastric cancer cell lines and these cell lines showed decreased ANXA10 expression by array based CGH and oligonucleotide microarray analysis. ANXA10 is a member of annexin family, and its function is not known clearly. To investigate whether ANXA10 might be a putative tumor suppressor gene, we performed functional analysis using small interfering RNA or expressional cDNA transfection in gastric cancer cell lines and demonstrated that ANXA10 inhibits gastric cancer cell growth. Furthermore, ANXA10 expression at the protein level was found to be reduced in 289/585 (49.4%) primary gastric cancer tissues. By univariate survival analysis, lack of ANXA10 expression was associated with poor survival (P = 0.016). Quantitative real-time PCR analysis validated loss of DNA at the ANXA10 locus in gastric carcinomas with reduced ANXA10 expression. These results suggest that inactivation by chromosomal loss of the ANXA10 leads to a loss of ANXA10 function, which may be a factor in gastric carcinogenesis.